IL271680B - Compositions and methods for inhibiting hmgb1 expression - Google Patents
Compositions and methods for inhibiting hmgb1 expressionInfo
- Publication number
- IL271680B IL271680B IL271680A IL27168019A IL271680B IL 271680 B IL271680 B IL 271680B IL 271680 A IL271680 A IL 271680A IL 27168019 A IL27168019 A IL 27168019A IL 271680 B IL271680 B IL 271680B
- Authority
- IL
- Israel
- Prior art keywords
- oligonucleotide
- seq
- nucleotides
- set forth
- hmgb1
- Prior art date
Links
- 230000014509 gene expression Effects 0.000 title claims description 60
- 239000000203 mixture Substances 0.000 title claims description 33
- 238000000034 method Methods 0.000 title description 27
- 230000002401 inhibitory effect Effects 0.000 title description 9
- 108091034117 Oligonucleotide Proteins 0.000 claims description 460
- 125000003729 nucleotide group Chemical group 0.000 claims description 277
- 239000002773 nucleotide Substances 0.000 claims description 251
- 101001025337 Homo sapiens High mobility group protein B1 Proteins 0.000 claims description 196
- 102100037907 High mobility group protein B1 Human genes 0.000 claims description 192
- 230000000692 anti-sense effect Effects 0.000 claims description 151
- 108091081021 Sense strand Proteins 0.000 claims description 96
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical group CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims description 75
- 230000000295 complement effect Effects 0.000 claims description 57
- 238000012986 modification Methods 0.000 claims description 57
- 235000000346 sugar Nutrition 0.000 claims description 50
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 49
- 230000008685 targeting Effects 0.000 claims description 49
- 239000003446 ligand Substances 0.000 claims description 39
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 23
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 15
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims description 12
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 10
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 6
- 206010008635 Cholestasis Diseases 0.000 claims description 5
- ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 0.000 claims description 5
- 208000027761 Hepatic autoimmune disease Diseases 0.000 claims description 4
- 230000001587 cholestatic effect Effects 0.000 claims description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 169
- 210000004027 cell Anatomy 0.000 description 79
- 108020004999 messenger RNA Proteins 0.000 description 69
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 56
- 230000009368 gene silencing by RNA Effects 0.000 description 56
- 230000004048 modification Effects 0.000 description 47
- 108020004707 nucleic acids Proteins 0.000 description 47
- 102000039446 nucleic acids Human genes 0.000 description 47
- 150000007523 nucleic acids Chemical class 0.000 description 46
- 210000004185 liver Anatomy 0.000 description 42
- 241000699670 Mus sp. Species 0.000 description 39
- 238000011282 treatment Methods 0.000 description 38
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 34
- 239000002953 phosphate buffered saline Substances 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 28
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 25
- 210000003494 hepatocyte Anatomy 0.000 description 24
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 24
- 238000011529 RT qPCR Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000007924 injection Substances 0.000 description 20
- 238000002347 injection Methods 0.000 description 20
- 208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- 238000007920 subcutaneous administration Methods 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 241000282414 Homo sapiens Species 0.000 description 14
- 238000011156 evaluation Methods 0.000 description 14
- 235000009200 high fat diet Nutrition 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 206010016654 Fibrosis Diseases 0.000 description 13
- 108020004459 Small interfering RNA Proteins 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 108010024636 Glutathione Proteins 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 229960003180 glutathione Drugs 0.000 description 11
- 208000006454 hepatitis Diseases 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 206010067125 Liver injury Diseases 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 108091028664 Ribonucleotide Proteins 0.000 description 10
- 230000004761 fibrosis Effects 0.000 description 10
- 231100000334 hepatotoxic Toxicity 0.000 description 10
- 150000002632 lipids Chemical class 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 239000002336 ribonucleotide Substances 0.000 description 10
- 239000004055 small Interfering RNA Substances 0.000 description 10
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 9
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000005547 deoxyribonucleotide Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 125000005647 linker group Chemical group 0.000 description 9
- 208000018191 liver inflammation Diseases 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 231100000753 hepatic injury Toxicity 0.000 description 8
- 230000003082 hepatotoxic effect Effects 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 125000002652 ribonucleotide group Chemical group 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 6
- 101710163270 Nuclease Proteins 0.000 description 6
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 108091007780 MiR-122 Proteins 0.000 description 5
- 108700011259 MicroRNAs Proteins 0.000 description 5
- 108091027967 Small hairpin RNA Proteins 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 230000003510 anti-fibrotic effect Effects 0.000 description 5
- 238000012230 antisense oligonucleotides Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000000423 cell based assay Methods 0.000 description 5
- 238000007385 chemical modification Methods 0.000 description 5
- 210000000172 cytosol Anatomy 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 108091051828 miR-122 stem-loop Proteins 0.000 description 5
- 239000002679 microRNA Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 101001090713 Homo sapiens L-lactate dehydrogenase A chain Proteins 0.000 description 4
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
- 102100034671 L-lactate dehydrogenase A chain Human genes 0.000 description 4
- URNSECGXFRDEDC-UHFFFAOYSA-N N-acetyl-1,4-benzoquinone imine Chemical compound CC(=O)N=C1C=CC(=O)C=C1 URNSECGXFRDEDC-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 150000002337 glycosamines Chemical class 0.000 description 4
- 210000004024 hepatic stellate cell Anatomy 0.000 description 4
- 102000053637 human HMGB1 Human genes 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 229960005489 paracetamol Drugs 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 150000004713 phosphodiesters Chemical class 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 3
- 108091023037 Aptamer Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101150003028 Hprt1 gene Proteins 0.000 description 3
- 241000282560 Macaca mulatta Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 3
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000013245 carbon tetrachloride model Methods 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 125000003636 chemical group Chemical group 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 231100000234 hepatic damage Toxicity 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000008818 liver damage Effects 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 2
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 108010002913 Asialoglycoproteins Proteins 0.000 description 2
- 101150008656 COL1A1 gene Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108700010013 HMGB1 Proteins 0.000 description 2
- 102000055207 HMGB1 Human genes 0.000 description 2
- 101150021904 HMGB1 gene Proteins 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 108010049606 Hepatocyte Nuclear Factors Proteins 0.000 description 2
- 102000008088 Hepatocyte Nuclear Factors Human genes 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 101100339426 Mus musculus Hmgb1 gene Proteins 0.000 description 2
- OVRNDRQMDRJTHS-JAJWTYFOSA-N N-acetyl-beta-D-galactosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-JAJWTYFOSA-N 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 102000013127 Vimentin Human genes 0.000 description 2
- 108010065472 Vimentin Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 101150084233 ago2 gene Proteins 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical group OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 239000013584 assay control Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- -1 is conjugated to 2 Chemical compound 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 150000002972 pentoses Chemical class 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000013424 sirius red staining Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 210000005048 vimentin Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- YCESYCIZPBRSAM-FNCVBFRFSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(3-nitropyrrol-1-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C=C([N+]([O-])=O)C=C1 YCESYCIZPBRSAM-FNCVBFRFSA-N 0.000 description 1
- AKLBZDKCJSROBD-FDYHWXHSSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(5-nitroindol-1-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CC=C([N+]([O-])=O)C=C2C=C1 AKLBZDKCJSROBD-FDYHWXHSSA-N 0.000 description 1
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 description 1
- WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000003930 C-Type Lectins Human genes 0.000 description 1
- 108090000342 C-Type Lectins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 101710106877 Collagen alpha-1(XIV) chain Proteins 0.000 description 1
- 102100024203 Collagen alpha-1(XIV) chain Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 102100029115 Fumarylacetoacetase Human genes 0.000 description 1
- 101150111020 GLUL gene Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101150003775 HNF1A gene Proteins 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 101150068639 Hnf4a gene Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100339424 Homo sapiens HMGB1 gene Proteins 0.000 description 1
- 101000780643 Homo sapiens Protein argonaute-2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 1
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100114688 Mus musculus Cyp3a11 gene Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 102100026466 POU domain, class 2, transcription factor 3 Human genes 0.000 description 1
- 101710084413 POU domain, class 2, transcription factor 3 Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 102000007584 Prealbumin Human genes 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100034207 Protein argonaute-2 Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100114680 Rattus norvegicus Cyp3a2 gene Proteins 0.000 description 1
- 108010057163 Ribonuclease III Proteins 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102000007238 Transferrin Receptors Human genes 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- VFRROHXSMXFLSN-KCDKBNATSA-N aldehydo-D-galactose 6-phosphate Chemical compound OP(=O)(O)OC[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C=O VFRROHXSMXFLSN-KCDKBNATSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000005068 bladder tissue Anatomy 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 235000020940 control diet Nutrition 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 108010022687 fumarylacetoacetase Proteins 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000007449 liver function test Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 125000000371 nucleobase group Chemical group 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002206 pro-fibrotic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000013417 toxicology model Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762526971P | 2017-06-29 | 2017-06-29 | |
| PCT/US2018/040410 WO2019006375A1 (en) | 2017-06-29 | 2018-06-29 | COMPOSITIONS AND METHODS FOR INHIBITING HMGB1 EXPRESSION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL271680A IL271680A (en) | 2020-02-27 |
| IL271680B true IL271680B (en) | 2022-09-01 |
Family
ID=64735107
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL271680A IL271680B (en) | 2017-06-29 | 2018-06-29 | Compositions and methods for inhibiting hmgb1 expression |
| IL295086A IL295086A (en) | 2017-06-29 | 2018-06-29 | Compositions and methods for inhibiting expression of hmgb1 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL295086A IL295086A (en) | 2017-06-29 | 2018-06-29 | Compositions and methods for inhibiting expression of hmgb1 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US10675295B2 (enExample) |
| EP (1) | EP3645013A4 (enExample) |
| JP (1) | JP2020529197A (enExample) |
| KR (1) | KR20200023427A (enExample) |
| CN (1) | CN111050776A (enExample) |
| AU (1) | AU2018294415A1 (enExample) |
| CA (1) | CA3068630A1 (enExample) |
| IL (2) | IL271680B (enExample) |
| MX (1) | MX2020000154A (enExample) |
| WO (1) | WO2019006375A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3068630A1 (en) | 2017-06-29 | 2019-01-03 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting hmgb1 expression |
| WO2019200124A1 (en) * | 2018-04-13 | 2019-10-17 | Dicerna Pharmaceuticals, Inc. | Double-stranded nucleic acid inhibitor molecules modified with tm-increasing nucleotides |
| KR20210127917A (ko) * | 2018-12-12 | 2021-10-25 | 다이서나 파마수이티컬, 인크. | 트리루프를 함유하는 이중-가닥의 핵산 억제제 분자 |
| IL284327B2 (en) * | 2018-12-28 | 2024-11-01 | Dicerna Pharmaceuticals Inc | Compositions and methods for inhibiting hmgb1 expression |
| WO2022221430A1 (en) * | 2021-04-14 | 2022-10-20 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for modulating pnpla3 expression |
| WO2022223515A2 (en) | 2021-04-19 | 2022-10-27 | Novo Nordisk A/S | Compositions and methods for inhibiting nuclear receptor subfamily 1 group h member 3 (nr1h3) expression |
| US20230107967A1 (en) * | 2021-08-25 | 2023-04-06 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting alpha-1 antitrypsin expression |
| TW202330920A (zh) * | 2021-12-01 | 2023-08-01 | 美商戴瑟納製藥股份有限公司 | 用於調節ａｐｏｃ３表現之組合物及方法 |
| TWI868755B (zh) * | 2022-06-24 | 2025-01-01 | 丹麥商諾佛 儂迪克股份有限公司 | 抑制跨膜絲胺酸蛋白酶６（ｔｍｐｒｓｓ６）表現的組成物及方法 |
| CN117264954A (zh) * | 2022-09-20 | 2023-12-22 | 北京福元医药股份有限公司 | 用于抑制hmgb1基因表达的双链核糖核酸及其修饰物、缀合物和用途 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2617426A1 (en) * | 2010-09-17 | 2013-07-24 | Japan Science and Technology Agency | Inhibitor of hmgb protein-mediated immune response activation, and screening method |
| WO2016100401A1 (en) * | 2014-12-15 | 2016-06-23 | Dicerna Pharmaceuticals, Inc. | Ligand-modified double-stranded nucleic acids |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7250496B2 (en) * | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
| CA2631212A1 (en) * | 2005-11-28 | 2007-07-05 | Medimmune, Llc | Antagonists of hmgb1 and/or rage and methods of use thereof |
| US8178503B2 (en) * | 2006-03-03 | 2012-05-15 | International Business Machines Corporation | Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes |
| US20110081362A1 (en) * | 2008-01-31 | 2011-04-07 | The Brigham And Women's Hospital, Inc. | Treatment of cancer |
| CA2738625C (en) * | 2008-09-22 | 2017-12-12 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for the specific inhibition of gene expression by dsrna possessing modifications |
| JP5582580B2 (ja) * | 2009-07-16 | 2014-09-03 | Ｎｅｃソリューションイノベータ株式会社 | Ｈｍｇｂ１結合核酸分子およびその用途 |
| WO2014028494A1 (en) | 2012-08-13 | 2014-02-20 | The Regents Of The University Of California | Detecting and treating liver damage |
| DK3204497T3 (da) * | 2014-10-10 | 2020-05-25 | Dicerna Pharmaceuticals Inc | Terapeutisk hæmning af lactatdehydrogenase og midler dertil |
| WO2017079227A1 (en) * | 2015-11-05 | 2017-05-11 | University Of Connecticut | Compositions and methods for the treatment of liver fibrosis |
| CN106244589A (zh) * | 2016-08-01 | 2016-12-21 | 中国人民解放军第四军医大学 | 靶向hmgb1基因的rna干扰片段及其应用 |
| CA3068630A1 (en) | 2017-06-29 | 2019-01-03 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting hmgb1 expression |
| WO2019126097A1 (en) * | 2017-12-18 | 2019-06-27 | Alnylam Pharmaceuticals, Inc. | High mobility group box-1 (hmgb1) irna compositions and methods of use thereof |
| US11751867B2 (en) | 2017-12-21 | 2023-09-12 | Cilag Gmbh International | Surgical instrument comprising sequenced systems |
| IL284327B2 (en) | 2018-12-28 | 2024-11-01 | Dicerna Pharmaceuticals Inc | Compositions and methods for inhibiting hmgb1 expression |
-
2018
- 2018-06-29 CA CA3068630A patent/CA3068630A1/en active Pending
- 2018-06-29 MX MX2020000154A patent/MX2020000154A/es unknown
- 2018-06-29 JP JP2019572382A patent/JP2020529197A/ja active Pending
- 2018-06-29 WO PCT/US2018/040410 patent/WO2019006375A1/en not_active Ceased
- 2018-06-29 EP EP18824412.3A patent/EP3645013A4/en active Pending
- 2018-06-29 IL IL271680A patent/IL271680B/en unknown
- 2018-06-29 CN CN201880056295.0A patent/CN111050776A/zh active Pending
- 2018-06-29 KR KR1020207002542A patent/KR20200023427A/ko not_active Ceased
- 2018-06-29 IL IL295086A patent/IL295086A/en unknown
- 2018-06-29 AU AU2018294415A patent/AU2018294415A1/en not_active Abandoned
- 2018-06-29 US US16/024,355 patent/US10675295B2/en active Active
-
2020
- 2020-04-30 US US16/863,081 patent/US11478501B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2617426A1 (en) * | 2010-09-17 | 2013-07-24 | Japan Science and Technology Agency | Inhibitor of hmgb protein-mediated immune response activation, and screening method |
| WO2016100401A1 (en) * | 2014-12-15 | 2016-06-23 | Dicerna Pharmaceuticals, Inc. | Ligand-modified double-stranded nucleic acids |
Non-Patent Citations (1)
| Title |
|---|
| GE, WEN-SONG, ET AL., INHIBITION OF HIGH-MOBILITY GROUP BOX 1 EXPRESSION BY SIRNA IN RAT HEPATIC STELLATE CELLS., 31 December 2011 (2011-12-31) * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL271680A (en) | 2020-02-27 |
| US20200297754A1 (en) | 2020-09-24 |
| US11478501B2 (en) | 2022-10-25 |
| IL295086A (en) | 2022-09-01 |
| US20190000870A1 (en) | 2019-01-03 |
| JP2020529197A (ja) | 2020-10-08 |
| AU2018294415A1 (en) | 2020-01-16 |
| CN111050776A (zh) | 2020-04-21 |
| MX2020000154A (es) | 2020-07-22 |
| WO2019006375A1 (en) | 2019-01-03 |
| KR20200023427A (ko) | 2020-03-04 |
| US10675295B2 (en) | 2020-06-09 |
| EP3645013A1 (en) | 2020-05-06 |
| CA3068630A1 (en) | 2019-01-03 |
| EP3645013A4 (en) | 2021-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7645323B2 (ja) | Ｂ型肝炎感染の治療方法 | |
| JP7476422B2 (ja) | Ｌｐａ発現を阻害するための組成物及び方法 | |
| US11478501B2 (en) | Compositions and methods for inhibiting HMGB1 expression | |
| JP7749645B2 (ja) | Ａｎｇｐｔｌ３発現を阻害する組成物及び方法 | |
| JP7357002B2 (ja) | 高コレステロール血症及び関連状態を治療するための、ｐｃｓｋ９を標的とするオリゴヌクレオチド | |
| US20250092403A1 (en) | Compositions and methods for inhibiting ketohexokinase (khk) | |
| US20220072024A1 (en) | Compositions and methods for inhibiting hmgb1 expression | |
| JP7453921B2 (ja) | Ｇｙｓ２発現を阻害するための組成物及び方法 | |
| US20220186229A1 (en) | Methods and compositions for inhibiting expression of cyp27a1 | |
| JP2024543195A (ja) | Ａｐｏｃ３発現を調節するための組成物及び方法 | |
| HK40028777A (en) | Compositions and methods for inhibiting hmgb1 expression |